POS0824 SAFETY AND EFFICACY OF THE INTENSIFIED B CELL DEPLETION INDUCTION THERAPY FOR PATIENTS WITH ANCA-ASSOCIATED VASCULITIS AND SEVERE RENAL INJURY: A CONTROLLED STUDY
Authors: D. Roccatello, S. Sciascia, S. Murgia, G. Quattrocchio, M. Ferro, E. De Simone, C. Naretto, A. Barreca, D. Rossi, R. Fenoglio
Journal: Annals of the Rheumatic Diseases (2022)

Background Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown to be an effective induction treatment for small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated. Objectives to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy compared to conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA) in patients with AAV and severe renal injury. Methods A cohort of 15 AAV patients with the most severe features of AVV renal involvement (as &lt;15 ml/min GFR and histological findings of paucimmune necrotizing glomerulonephritis with more than 50% crescents of non-sclerotic glomeruli at the renal biopsy) was treated IBCDT and compared to compared toa control group of 10 patients with AAV treated with a conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA). Independently on the pharmacologic regimen, plasma exchange (7 procedures with 1-1.5 plasma volume replacement) was performed in the presence of 1. alveolar haemorrhage, and 2. more than 50% florid crescents in the nonsclerotic glomeruli, or 3. dialysis dependence. Results Complete clinical remission (BVAS 0) was observed at 6 months in 14 of 15 patients (93%). All cases treated with IBCDT who achieved a complete clinical remission experienced a depletion of peripheral blood B cells at the end of therapy. Of the 10 dialysis dependent patients at onset, 6 subjects (60%) experienced a functional recovery allowing the suspension of dialysis treatment. When compared to the control group, no statistically significant difference was observed in patients treated with IBCDT in terms of overall survival, 6-month therapeutic response rate, and 6-, and 12-month functional renal recovery. The cumulative total dose of CYC in the case group was on average 1 g/patient while in the control group on average 8.5 g / patient (p = 0.00008). Plasmapheresis sessions were performed at part of the induction therapy among 13 patients (87%) in the case group and 8 (80%) in the control group. Conclusion The results of this study showed that IBCDT appeared to be safe and has the same efficacy profile when compared to conventional therapy with CYC plus AZA in the management of the most severe patients with AAV. Additionally, this avoids the need of prolonged maintenance therapy for long, and limits the exposure to CYC with consequent reduced toxicity and drug-related side effect rates. Disclosure of Interests None declared